Breast cancer is the most common cancer in women, and among malignant diseases in women, it is the biggest killer. Both hormonal therapy and chemotherapy play a very large role in the treatment of patients with breast cancer, and both forms of therapy have been effective in the palliation of patients with Stage IV disease. Unfortunately, almost all remissions are partial remissions. Complete remissions are infrequent (10-15 percent) and cure in Stage IV breast cancer is virtually nonexistent. Breast tumors are known to be heterogeneous with respect to estrogen receptor status, and this biochemical heterogeneity may account for the low complete remission rate. Empirical combination of hormonal therapy and chemotherapy have only slightly increased the overall remission rate and have not altered the complete remission rate. Over the past few years, clinical scientists have started to investigate newer methods of combining chemotherapy and hormonal therapy. One area of this research involves the stimulation of breast cancers by hormones or growth factors in order to make these tumors potentially more sensitive to cytotoxic chemotherapy. In this application, we present a vast amount of Pilot Data from a clinical study aimed at testing this hypothesis. The clinical results from this pilot study are promising and we feel need to be expanded. Furthermore, we will attempt to correlate these clinical response data with in vivo measurements of tumor growth. The expanded clinical study, in addition to the sequential in vivo measurements on tumors from patients with breast cancer, is the first phase of this application. Phase II of this application will consist of in vivo measurement of tumor growth in women with breast cancer who will receive potential stimulation of their tumors from estrogen, insulin and a combination of estrogen and insulin. It is our aim to attempt to maximally stimulate tumor growth to potentiate the effects of subsequent cytotoxic chemotherapy. Our overall goal is the design and testing of a second generation protocol utilizing this stimulation hypothesis.